Genital tract infections threaten the health of young women, their sexual partners and their infants causing a host of diseases and costing billions of U.S. health care dollars. The research emphasis on genital tract infections has been directed toward pathogenesis of these diseases and their associated pathogens. Little is known about the biology of the host immune response at the cervico-vaginal junction, which is the portal of entry for all sexually transmitted pathogens. We hypothesize that there are cyclic changes in the mucosal immune competence of the genital tract which combined with the local immunosuppressive effects of semen will expose women to a greater risk of acquiring sexually transmitted infections. The goal of these studies is to l) evaluate the influence of ovarian steroid hormones on mucosal immunity in the genital tract; 2) establish a model of normal immune competence in cycling women; and 3) evaluate changes in immunocompetence induced by the introduction of exogenous factors into the vagina. The effect of ovarian steroid hormone levels on humoral and cellular immunity in the genital tract will be determined by measuring several immune parameters in women either during the normal menstrual cycle, while on oral contraceptives, or during estrogen replacement therapy. After determining normal immune parameters in cycling women, in vivo changes in these parameters will be assessed following semen deposition or the use of vaginal spermicides. The studies outlined in specific aims l and 2 examine general immune parameters to establish the potential immune responsiveness of the genital tract. Specific aim 3 is designed to examine antigen specific responses in the genital tract and the effects of semen or spermicide on vaccine-induced immune responses. The data generated by these studies will aid medical professionals who counsel women about sexually transmitted diseases by providing evidence of potential factors influencing susceptibility to infection. These studies have the potential to not only impact the field of infectious diseases, but also the fields of public health and contraception.